Bile acid hormone
Ileal FGF19 signaling
Also searched as Ileal FGF19 signaling.
You want it signaling: healthy FGF19 tone quiets hepatic glucose output after eating, easing the glycemic load.
In depth
The post-meal hormone released by the ileum that tells the liver to stand down glucose production — an insulin-independent gut-to-liver dispatch.
What drives it
Gut barrier increases it.
Bile-acid/FXR–FGF19 review (PMC4465534) — bile acids activate FXR in ileal enterocytes to induce the enterohepatic hormone FGF15/19. PMC4465534. Mechanism: gut bacteria convert primary bile acids into secondary bile acids, which activate intestinal FXR; FXR then induces FGF19 in humans (FGF15 in mice) and SHP, and together these suppress CYP7A1, the rate-limiting enzyme of de novo bile-acid synthesis — a feedback signal from gut to liver. Loss-of-function is decisive and it is the microbiota that matters: in germ-free or antibiotic-treated mice, taurine-conjugated beta-muricholic acid accumulates; TbetaMCA is an FXR antagonist, and its accumulation reduced Fgf15 expression and raised Cyp7a1. Reduced bile-salt hydrolase activity likewise diminished secondary bile acids and inhibited FXR signaling. FGF19 in humans, FGF15 in mice — they are orthologues, not the same molecule. And inhibiting intestinal FXR altered bile-acid composition and decreased obesity incidence in mice, so more FXR signaling is not straightforwardly better. PMC4465534
What it drives
It reduces Lowers liver sugar.
Potthoff 2011, Cell Metab 13:729 — FGF15/19 represses hepatic gluconeogenesis by inhibiting the CREB–PGC-1α pathway (lowering PEPCK and G6Pase), independent of insulin. Human liver biopsies with a striking threshold: in class-III obese patients undergoing bariatric surgery, those with type 2 diabetes had lower serum FGF19 and higher FGF21; and when FGF19 was below 200 and FGF21 above 500, 91 percent of patients had diabetes. The signaling arm is intact too — FGF19 acts through FGFR4 and beta-klotho in hepatocytes, and CYP7A1, beta-Klotho, FGFR4 and HNF4-alpha expression differed between patients who did and did not remit diabetes after surgery. But the evidence here is cross-sectional and CASE/CONTROL: it establishes that FGF19 is low in diabetes and that the pathway is dysregulated, not that FGF19 directly represses gluconeogenic transcription. That specific step is asserted in the wider literature but is not demonstrated in the source read here. Treat the direction as supported, the mechanism as not yet evidenced at this pathway.
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.